Glial cell proteome using targeted quantitative methods for potential multi-diagnostic biomarkers

Glioblastoma is one of the most malignant primary brain cancer. Despite surgical resection with modern technology followed by chemo-radiation therapy with temozolomide, resistance to the treatment and recurrence is common due to its aggressive and infiltrating nature of the tumor with high proliferation index. The median survival time of the patients with glioblastomas is less than 15 months. Till now there has been no report of molecular target specific for glioblastomas. Early diagnosis and development of molecular target specific for glioblastomas are essential for longer survival of the patients with glioblastomas. Development of biomarkers specific for glioblastomas is most important for early diagnosis, estimation of the prognosis, and molecular target therapy of glioblastomas. To that end, in this study, we have conducted a comprehensive proteome study using primary cells and tissues from patients with glioblastoma. In the discovery stage, we have identified 7429 glioblastoma-specific proteins, where 476 proteins were quantitated using Tandem Mass Tag (TMT) method; 228 and 248 proteins showed up and down-regulated pattern, respectively. In the validation stage (20 selected target proteins), we developed quantitative targeted method (MRM: Multiple reaction monitoring) using stable isotope standards (SIS) peptide. In this study, five proteins (CCT3, PCMT1, TKT, TOMM34, UBA1) showed the significantly different protein levels (t-test: p value ≤ 0.05, AUC ≥ 0.7) between control and cancer groups and the result of multiplex assay using logistic regression showed the 5-marker panel showed better sensitivity (0.80 and 0.90), specificity (0.92 and 1.00), error rate (10 and 2%), and AUC value (0.94 and 0.98) than the best single marker (TOMM34) in primary cells and tissues, respectively. Although we acknowledge that the model requires further validation in a large sample size, the 5 protein marker panel can be used as baseline data for the discovery of novel biomarkers of the glioblastoma.This work was supported by Institute of Information & communications Technology Planning & Evaluation (IITP) grant funded by the Korea government (MSIT) (No. NRF-2017M3A9G4052982, NRF-2022M3A9G8082637) This research was partly supported by the Bio & Medical Technology Development Program of the National Research Foundation (Grant Nos. 2015M3C7A1028926 & 2020M3A9G8022029); the National Research Foundation of Korea Grant (Grant No. NRF2017M3C7A1047392) of the Ministry of Science and ICT, Republic of Korea; the Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program (KGM456212109816); Electronics and Telecommunications Research Institute (ETRI) grant funded by the Korean government (21YB1500); Soonchunhyang University Research Fund; the National Research Foundation of Korea (NRF) grant funded by the Korea government(MSIT) (No. 2023R1A2C200769911). H.J. Oh was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1C1C1011255) and a Korea University Gran

Development of Oxidative Cascade Synthesis of Heterocycles

Department of ChemistryThe construction of new bonds for carbon-carbon or carbon-heteroatom has emerged as a readily accessible pathway for elaborate structures in various methods. While transition metal catalysis has been widely utilized in conventional reactions, metal-free strategies are revealed as alternatives to overcome challenges: expensiveness, removal of toxic metal residue, and pre-functionalization. As useful synthetic intermediates, radical species facilitate transformations including bond formation and cyclization. Metal-free oxidative cascade reactions for versatile heterocycles were described. In chapter 1, iodine-mediated oxidative cycloaddition was represented for dihydropyrano[4,3-b]indoles and 2,3-dihydrofurans. Following charge-accelerated single electron transfer between equimolar amounts of partners, highly selective radical-radical cross-coupling was conducted through solvent cage effect. The coupled intermediate undergoes distinct ways depending on the substrates. Indole-derived intermediate gives indolopyran via second oxidation and 6???-electrocyclization. On the other hand, enamine-derived intermediate produces stereoselective 2,3-dihydrofurans by oxa-Michael addition. In chapter 2, photoredox cycloaddition of imino-alkynes and alkenes for bicyclic N-heterocycles was described in a redox neutral manner. Subsequent ring-opening of azetine intermediate and photocatalytic rearrangement furnish pyrrolizidinones and indolizidinone via intramolecular [2+2] cyclization between imine and alkynes. These bicyclic heterocycles could be transformed into pyrrolizidine scaffolds. Otherwise, for imine and alkenes, intramolecular [4+2] cyclization involving the carbonyl group of ester provides dihydro-1,4-oxazine derivatives.clos

Get Out

Team BBB\u27s short film Get Out placed 1st out of 300 entries in the 24 HOURS Animation contest hosted by California State University, Long Beach. The annual competition challenges students to produce a 30-second animated film within 24 hours of learning what the film\u27s topic should be. Team BBB\u27s topic was to predict the future 100 years forward

Hierarchical Optimization of High-Performance Biomimetic and Bioinspired Membranes

Biomimetic and bioinspired membranes have emerged as an innovative platform for water purification and aqueous separations. They are inspired by the exceptional water permeability (∼10 9 water molecules per second per channel) and perfect selectivity of biological water channels, aquaporins. However, only few successes have been reported for channel-based membrane fabrication due to inherent challenges of realizing coherence between channel design at the angstrom level and development of scalable membranes that maintain these molecular properties at practice-relevant scales. In this article, we feature recent progress toward practical biomimetic membranes, with the review organized along a hierarchical structural perspective that biomimetic membranes commonly share. These structures range from unitary pore shapes and tubular hydrophobic channel geometries to self-assembled bilayer structures and finally to macroscale membranes covering a size range from the angstrom, to the micrometer scale, and finally to the centimeter and larger scales. To maximize the advantage of water channel implementation into membranes, each feature needs to be optimized in an appropriate manner that provides a path to successful scale-up to achieve high performance in practical biomimetic and bioinspired membranes. © 2018 American Chemical Society.11Nsciescopu

Metal-Free Synthesis of Indolopyrans and 2,3-Dihydrofurans Based on Tandem Oxidative Cycloaddition

The synthesis of versatile scaffold indolopyrans based on C-C radical-radical cross-coupling under metal-free conditions is described. The reaction involving single electron transfer between coupling partners followed by cage collapse allows highly selective cross-coupling while employing only equimolar amounts of coupling partners. Moreover, the mechanistic manifold was expanded for the functionalization of enamines to give the stereoselective synthesis of 2,3-dihydrofurans. This iodine-mediated oxidative coupling features mild conditions and fast reaction kinetics

Synthesis of Bicyclic N-Heterocycles via Photoredox Cycloaddition of Imino-Alkynes and Imino-Alkenes

Cycloaddition reactions offer great advantages regarding atom and step economy for the construction of various carbocycles and heterocycles. While the recent development based on sensitized visible light photocatalysis allowed the synthesis of azetidines via imine-alkene [2 + 2] cycloaddition, imine-alkyne [2 + 2] cycloaddition under visible light photocatalysis has not been reported. In this regard, we report the synthesis of pyrrolizidinones based on intramolecular imine-alkyne [2 + 2] cycloaddition under visible light photocatalysis. This redox-neutral reaction involves formal imine-alkyne metathesis followed by redox-mediated annulation with concomitant rearrangement. In contrast, the use of imino-alkenes provides dihyro-1,4-oxazines via an alternative [4 + 2] cycloaddition pathway. The proposed reaction mechanisms were supported by control experiments and DFT calculations

Hierarchical Optimization of High-Performance Biomimetic and Bioinspired Membranes

Biomimetic and bioinspired membranes have emerged as an innovative platform for water purification and aqueous separations. They are inspired by the exceptional water permeability (∼10 9 water molecules per second per channel) and perfect selectivity of biological water channels, aquaporins. However, only few successes have been reported for channel-based membrane fabrication due to inherent challenges of realizing coherence between channel design at the angstrom level and development of scalable membranes that maintain these molecular properties at practice-relevant scales. In this article, we feature recent progress toward practical biomimetic membranes, with the review organized along a hierarchical structural perspective that biomimetic membranes commonly share. These structures range from unitary pore shapes and tubular hydrophobic channel geometries to self-assembled bilayer structures and finally to macroscale membranes covering a size range from the angstrom, to the micrometer scale, and finally to the centimeter and larger scales. To maximize the advantage of water channel implementation into membranes, each feature needs to be optimized in an appropriate manner that provides a path to successful scale-up to achieve high performance in practical biomimetic and bioinspired membranes. © 2018 American Chemical Society.11Nsciescopu

Risk and Outcome of Infective Endocarditis in Streptococcal Bloodstream Infections according to Streptococcal Species

ABSTRACT This study aimed to identify which streptococcal species are closely associated with infective endocarditis (IE) and to evaluate risk factors for mortality in patients with streptococcal IE. We performed a retrospective cohort study of all patients with streptococcal bloodstream infection (BSI) from January 2010 to June 2020 in a tertiary hospital in South Korea. We compared clinical and microbiological characteristics of streptococcal BSIs according to the diagnosis of IE. We performed multivariate analysis to evaluate the risk of IE according to streptococcal species and risk factors for mortality in streptococcal IE. A total of 2,737 patients were identified during the study period, and 174 (6.4%) were diagnosed with IE. The highest IE prevalence was in patients with Streptococcus mutans BSI (33% [9/27]) followed by S. sanguinis (31% [20/64]), S. gordonii (23% [5/22]), S. gallolyticus (16% [12/77]), and S. oralis (12% [14/115]). In multivariate analysis, previous IE, high-grade BSI, native valve disease, prosthetic valve, congenital heart disease, and community-onset BSI were independent risk factors for IE. After adjusting for these factors, S. sanguinis (adjusted OR [aOR], 7.75), S. mutans (aOR, 5.50), and S. gallolyticus (aOR, 2.57) were significantly associated with higher risk of IE, whereas S. pneumoniae (aOR, 0.23) and S. constellatus (aOR, 0.37) were associated with lower risk of IE. Age, hospital-acquired BSI, ischemic heart disease, and chronic kidney disease were independent risk factors for mortality in streptococcal IE. Our study points to significant differences in the prevalence of IE in streptococcal BSI according to species. IMPORTANCE Our study of risk of infective endocarditis in patients with streptococcal bloodstream infection demonstrated that Streptococcus sanguinis, S. mutans, and S. gallolyticus were significantly associated with higher risk of infective endocarditis. However, when we evaluated the performance of echocardiography in patients with streptococcal bloodstream infection, patients with S. mutans and S. gordonii bloodstream infection had a tendency of low performance in echocardiography. There are significant differences in the prevalence of infective endocarditis in streptococcal bloodstream infection according to species. Therefore, performing echocardiography in streptococcal bloodstream infection with a high prevalence of, and significant association with, infective endocarditis is desirable

Dehydrated Biomimetic Membranes with Skinlike Structure and Function

Novel vapor-permeable materials are sought after for applications in protective wear, energy generation, and water treatment. Current impermeable protective materials effectively block harmful agents but trap heat due to poor water vapor transfer. Here we present a new class of materials, vapor permeable dehydrated nanoporous biomimetic membranes (DBMs), based on channel proteins. This application for biomimetic membranes is unexpected as channel proteins and biomimetic membranes were assumed to be unstable under dry conditions. DBMs mimic human skin’s structure to offer both high vapor transport and small molecule exclusion under dry conditions. DBMs feature highly organized pores resembling sweat pores in human skin, but at super high densities (>1012 pores/cm2). These DBMs achieved exceptional water vapor transport rates, surpassing commercial breathable fabrics by up to 6.2 times, despite containing >2 orders of magnitude smaller pores (1 nm vs >700 nm). These DBMs effectively excluded model biological agents and harmful chemicals both in liquid and vapor phases, again in contrast with the commercial breathable fabrics. Remarkably, while hydrated biomimetic membranes were highly permeable to liquid water, they exhibited higher water resistances after dehydration at values >38 times that of commercial breathable fabrics. Molecular dynamics simulations support our hypothesis that dehydration induced protein hydrophobicity increases which enhanced DBM performance. DBMs hold promise for various applications, including membrane distillation, dehumidification, and protective barriers for atmospheric water harvesting materials